This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Inhibitors of miR122 have recently been shown to reduce HCV viral load by up to 2.6 logs in HCV infected chimpanzees. Analysis of hepatic gene expression revealed that the drop in viremia was accompanied by a reduction in the levels of hepatic transcripts for interferon stimulated genes (ISGs) or the normalization of the IFN pathway. HCV chronically infected chimpanzees do not exhibit an antiviral response to exogenous IFN[unreadable] and resemble null responders in the human population in this regard. The null response phenotype in chimpanzees and in man correlates with elevated hepatic ISG expression, while IFN responders have low baseline ISG transcript levels. Thus, the reduction in ISG transcript levels during therapy with miR122 inhibitors likely results in the conversion of the null IFN phenotype to the responder phenotype. This study is designed to directly test this concept and to demonstrate that IFN[unreadable] induces hepatic ISG expression and an antiviral effect in chimpanzees treated with miR122 inhibitors.